Effects of hypothyroidism and cholesterol feeding on the clearance of chylomicron remnants in vivo and by rat hepatocyte monolayers.
The hepatic catabolism of chylomicron remnants in normal rats and in hypothyroid rats which were either normocholesterolaemic or made hypercholesterolaemic by feeding cholesterol and cholic acid was studied in vivo and in hepatocyte monolayers. In vivo, the clearance of injected chylomicron remnants labelled with either cholesteryl- or retinyl ester was delayed in the hypercholesterolaemic hypothyroid rats, but not in normocholesterolaemic hypothyroid rats. Cholesteryl-ester-rich hepatocytes from hypercholesterolaemic hypothyroid rats took up remnants less efficiently than did normal hepatocytes. Hepatocytes from normocholesterolaemic hypothyroid rats had a lower cholesteryl ester content and took up remnant particles to a greater degree than did normal hepatocytes. When normal hepatocytes were incubated with hypercholesterolaemic serum or with mevalonolactone, which increased cell cholesteryl ester content, there was a slight suppression of remnant uptake. Also, addition of triiodothyronine to hepatocyte monolayers suppressed rather than increased uptake of chylomicron remnants in hepatocytes. Thus, the study suggests that chylomicron remnant uptake by the liver is not inhibited by hypothyroidism per se but by the cholesterol accumulation in hepatocytes that is the consequence of cholesterol and bile acid feeding of the rats. Although the cholesteryl ester content in hepatocytes seems to determine remnant uptake, the regulation of uptake does not seem to be as effective as that of the LDL receptor in extrahepatic cells.
D000818:Animals; D002478:Cells, Cultured; D002791:Cholesterol, Dietary; D002793:Cholic Acids; D002914:Chylomicrons / Q000378:metabolism*; D006937:Hypercholesterolemia / Q000209:etiology / Q000378:metabolism*; D007037:Hypothyroidism / Q000378:metabolism*; D066298:In Vitro Techniques; D007783:Lactones / Q000494:pharmacology; D008099:Liver / Q000166:cytology / Q000378:metabolism*; D008798:Mevalonic Acid / Q000031:analogs & derivatives / Q000494:pharmacology; D051381:Rats; D012710:Serum Albumin, Bovine / Q000494:pharmacology
D002791:Cholesterol, Dietary; D002793:Cholic Acids; D002914:Chylomicrons; D007783:Lactones; D012710:Serum Albumin, Bovine; C015367:mevalonolactone; D008798:Mevalonic Acid